Abstract
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dys-regulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation gene expression mediated by the transcription factor NF-κB is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-κB -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-κB up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3- kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dys-regulated basal NF-κB activity may contribute to the mild pro-inflammatory state of aging.
Original language | English (US) |
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Pages (from-to) | 957-974 |
Number of pages | 18 |
Journal | Aging |
Volume | 6 |
Issue number | 11 |
State | Published - 2014 |
Externally published | Yes |
Keywords
- CD4+ T cells
- Gene expression
- Human aging
- NF-κB
- PI3K
ASJC Scopus subject areas
- Aging
- Cell Biology